Newer Antipsychotics No Better in Kids

Older Drug Works as Well as New Drugs, and Without the Weight Gain, Study Shows

From the WebMD Archives

Sept. 15, 2008 -- Widely prescribed, newer-generation antipsychotic drugs are no more effective for the treatment of schizophrenia in children and teens than older, cheaper drugs, a government-funded study shows.

Under the direction of the National Institute of Mental Health (NIMH), researchers compared two of the newer drugs, known as atypical antipsychotics, to an older-generation antipsychotic.

They found no major differences in treatment outcomes, but big differences in side effects among young patients taking the newer and older drugs.

The findings are similar to a larger NIMH study in adults with schizophrenia, published in 2005.

Weight Gain With Zyprexa

Children and teens who took the newer drugs Zyprexa and risperidone gained about 13 pounds and 8 pounds, respectively, during the two-month treatment part of the study.

The Zyprexa-treated patients also experienced increases in total cholesterol, LDL "bad" cholesterol, insulin, and liver enzymes. Such metabolic side effects in addition to risk for obesity "generate considerable long-term risks for diabetes and cardiovascular disease," the researchers noted.

The patients who took the older antipsychotic drug molindone (also known as Moban) experienced no weight gain, but did have more akathisia (movement disorder involving restlessness and need to fidget).

"All three of these drugs have different side effect profiles, but the newer drugs are much more likely to cause weigh gain," says psychiatrist and study researcher Linmarie Sikich, MD of the University of North Carolina.

Sikich points out that almost all children and adolescents now treated for schizophrenia start treatment on the newer, atypical drugs.

She adds that the American Academy of Child and Adolescent Psychiatry (AACAP) -- the nation's leading pediatric mental health organization -- recommends the second-generation drugs as the first-line treatment for schizophrenia in children and teens.

"At the very least, we think these results mean AACAP needs to revisit these guidelines," she says.

Erin Baker, a spokeswoman for AACAP, tells WebMD that the group is doing just that.

"We are currently revising our practice parameter for schizophrenia and will take into account all data, including this new information," Baker tells WebMD.

Zyprexa Manufacturer Responds

A spokesman for Zyprexa manufacturer Eli Lilly says the new study paints an incomplete picture of the side effect profile of molindone and other first-generation drugs.


The second-generation drugs were developed in large part to avoid these side effects, which can include tics, rigidity, and even an irreversible, Parkinson's-like syndrome that can be crippling.

Jamaison Schuler of Eli Lilly tells WebMD that the eight-week treatment arm of the study was far too short to assess the risk for the well established, long-term side effects.

"Physicians balance such potentially disabling and irreversible movement disorders associated with many first-generation antipsychotics with the potential metabolic adverse events associated with the second-generation drugs when considering what therapy is best for each patient," he says.

The patients in the study who took the first-generation drug also took another drug used to reduce these movement-related side effects, which is a common treatment practice.

The study included 116 children and teens aged 8-19 who had been diagnosed with early-onset schizophrenia spectrum disorder (EOSS).

After eight weeks of treatment, 50% of the study participants taking molindone showed improvement in schizophrenia symptoms, compared to 46% of patients taking risperidone and 34% of patients on Zyprexa. There were no statistically significant differences among the improvements seen in the three different groups.

The study is published online in the latest issue of the American Journal of Psychiatry.

Although schizophrenia is not commonly found in children under 12, the Department of Health & Human Services estimates it occurs in about three out of every 1,000 adolescents.

Newer Antispychotics vs. Older Antispychotics

NIMH chief of child psychiatry Judith Rapoport, MD, agrees that the study was too small and the treatment arm too short to capture the full side effect profile of the older-generation drugs.

But she adds that periodically taking patients off molindone and other older antipsychotic treatments can help mitigate the risk for permanent side effects.

"The pendulum has probably swung too far in the direction of the newer generation of drugs," Rapoport tells WebMD. "There are probably children who would be better off taking a low-dose of a first-generation drug instead of a second-generation drug, especially if they gain a lot of weight on these newer drugs."

NIMH director Thomas Insel, MD, tells WebMD that the new study and the earlier trial in adults illustrate the need for better antipsychotic drugs.


At best, only half of the patients in the study responded to the medication they were on. And just 10% to 20% of the patients continued treatment for a full year.

"We really need a new era of drug development for psychotic illness, both in children and adults," Insel says. "These studies remind us that we are not where we want to be in the treatment of psychosis. There are just too many people who aren't getting better."

Teva Pharmaceuticals, the maker of generic risperidone, was contacted but WebMD did not receive comment by publication time.

WebMD Health News Reviewed by Louise Chang, MD on September 15, 2008



Sikich, L. American Journal of Psychiatry, online edition, Sept. 15, 2008.

Linmarie Sikich, MD, associate professor of psychiatry, University of North Carolina at Chapel Hill.

Thomas R. Insel, MD, director, National Institute of Mental Health, Bethesda, Md.

Judith Rapoport, MD, practicing child psychiatrist and chief of child psychiatry branch, NIMH, Bethesda, Md.

Erin Baker, spokeswoman, American Academy of Child and Adolescent Psychiatry.

Jamaison Schuler, spokesman, Eli Lilly and Company.

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